Evolution of theranostics – Going beyond radioiodine therapy

Theranostics – the combination of diagnostic imaging with targeted therapy – is becoming widely implemented all over the world. The field of theranostics combines molecular imaging (primarily PET and SPECT) with targeted radionuclide therapy, which involves the use of small molecules, peptides and/or antibodies as carriers for therapeutic radionuclides, typically those emitting α-, β- or auger-radiation.

Growth of theranostics in India
The growth of theranostics in India can be attributed to the increasing prevalence of cancer, rising geriatric population, and growing availability of PET (positron emission tomography) imaging centers in India, development of advanced radiopharmaceuticals in India, and rising awareness regarding early diagnosis and treatment of diseases. Furthermore, favorable government initiatives, such as Make in India scheme are likely to propel the industry growth in future.

In India, the burden of cancer is rising, and today we witness an exponential growth of nuclear medicine radio-theranostics. What started with 131I in Graves’ disease and thyroid cancer, has today evolved to the era of theranostics with not just beta- but alpha-therapy as well. Theranostics-based nuclear-targeted therapies are emerging as a useful tool for treating patients suffering from advanced prostate carcinoma, neuroendocrine, and gastroenteropancreatic tumors, such as neuroblastomas and several other refractory malignancies.

Over the past few years, several major clinical, commercial, and regulatory developments have been registered in the nuclear medicine market. Some of the key developments in the segment from recent years are:

• In October 2021, the US FDA issued a study may proceed letter to Curium to begin its Phase-III trial with lutetium Lu 177 PSMA I&T.
• In February 2022, Applied Molecular Therapies launched 177Lu PSMATherapy for treating prostate cancer.
• In March 2022, Bracco Imaging launched Blue Earth Therapeutics to advance the development of therapeutic radiopharmaceutical technology.
• Approvals of new radiotheranostic agents, such as ¹⁷⁷Lu-DOTATATE and ¹⁷⁷Lu-PSMA-617, alongside the availability of companion diagnostic agents (such as ⁶⁸Ga-DOTATATE and ⁶⁸Ga-PSMA-11, respectively) have driven a resurgence of interest in the field that is driving numerous clinical trials testing novel radiotheranostics.
• Currently, Lu-177 is produced in India by the Board of Radiation and Isotope Technology (BRIT), which is an industrial unit of the Department of Atomic Energy (DAE), Government of India, and peptides like DOTATATE and PSMA are available in a kit form indigenously.
• Actinium-225 (Ac-225), labeled PSMA-617, is being made available as a unit patient dose from overseas and the labeling with PSMA is being carried out in individual hospital-based radiopharmacies for the treatment of mCRPC, which is also being performed in few institutions in India with promising initial results.

Outlook
The exponential, global expansion of theranostics in oncology stems from its potential to target and eliminate tumor cells with minimal adverse effects, owing to a mechanism of action that differs distinctly from that of most other systemic therapies. Currently, an enormous opportunity exists to expand the number of patients, who can benefit from this technology, to address the urgent needs of many thousands of patients across the world. Although there are challenges ahead, by investing in the infrastructure of radionuclide production; committing to train and nurture the next generation of nuclear medicine researchers, technicians, and clinicians; and developing a program that will sustain nuclear medicine research, we will all reap the benefits of a better healthcare.